A Multimodal Mass Spectrometric Imaging Instrument with Enhanced Ion Characterisation Capability

Lead Research Organisation: Rosalind Franklin Institute
Department Name: Research


This challenge led community project has a clear mission to create new mass spectrometry instrumentation for sensitive, rapid and spatially resolved detection and structural characterisation of exogenous and endogenous compounds from complex samples (e.g. prokaryotic and eukaryotic cells and tissues). The new instruments will include novel multi-modal ion sources with post-desorption ionisation, coupled to a configuration of mass analysers, designed to deliver the highest accuracy and selectivity, which has not been attempted or achieved before.

We will construct a unique multimodal imaging mass spectrometer instrument, which allows the molecular mapping of biological tissues at unprecedented sensitivity, chemical depth and spatial resolution. The main instrument modules include a Fourier-transform Ion Cyclotron Resonance spectrometer and hybrid trapped ion mobility-high-resolution time-of-flight mass analyser (instrument 1), a secondary ion mass spectrometer with post-ionisation (instrument 2), and a microscope mode SIMS instrument (instrument 3).

To develop the components to deliver this we have designed seven collaborative projects, hosted at partners sites Imperial College London, Oxford, Birmingham and Manchester supported by collaborations with partner institutes Leeds and Edinburgh and collaborating partners Bruker, Ionoptika, NPL and AstraZeneca.

Planned Impact

The project will put the Rosalind Franklin Institute at the focal point of tissue-based systems biology research in the UK. The new capability will benefit biological and biomedical communities, providing hitherto unavailable information about the chemical composition of cellular structures detected by optical or electron microscopic methods. New methods for structural elucidation combined with the most comprehensive and most sensitive molecular imaging instrument will be a powerful new approach for studying fundamental biology, environmental exposure and metabolic interaction between different species (e.g. host-microbiota interactions).
In order to deliver this impact to academic communities, we will start the chemical imaging and associated structure elucidation of unknown chemical species focusing on spectral features detected in earlier studies and reporting this highly sought-after information to our past and present collaborators. The academic research groups associated with the Franklin have analysed thousands of tissue samples by a wide variety of mass spectrometric imaging (MSI) methods. We estimate that > 1500 components showed biological significance but database-driven identification was unsuccessful. Providing this fundamentally new information for the pharmacology, molecular biology and biomedical research groups in the UK will lead to the discovery of yet undescribed metabolic processes, elucidation of disease aetiologies at the molecular level, understanding the nature and mechanism of environmental exposures including dietary factors and the physiological and pathophysiological role of host-associated microbial communities among others.
We are planning to expand our collaboration network through regular Franklin Seminars organised at the Member Institutions, local workshops organised by the Member BMS theme leads and at MSI-themed meetings including the annual meeting of the British MS Society (BMSS) and the MSI Special Interest Group meeting (BMSS). The new instrument and the facility will be made available for researchers across the UK. Time will be allocated for proof-of-concept experiments, while in case of larger projects the RFI will serve as a co-applicant for proposals submitted to potential funders including UKRI and charities.
The majority of MSI studies are aimed at the identification of systems-level differences between diseased and healthy tissues/cells to understand disease mechanism and define novel diagnostic and prognostic markers. Unfortunately, the structure elucidation of detected features poses a serious bottleneck at the translation and utilization of these markers. By lifting this constraint, hundreds of new, tissue-derived biomarkers will enter into the translational pipeline, resulting in the early, pre-symptomatic detection of chronic diseases including various types of cancer, cardiovascular diseases, diabetes and dementia among others. Parallel detection and quantification of these markers is feasible using MSI systems - redefining the histopathology landscape, shifting from the diagnosis of late stage diseases to the screening of early stage disease or even the identification of elevated risk factors. We are planning the deliver this impact through our existing translational pipeline comprising the NIHR-funded Biomedical Research Centre Network (Eight of the Member Institutes host BRCs) delivering clinical studies and validation trials and the NHS Northwest London Pathology services introducing the new assays with availability across the entire NHS. We have been developing this pipeline with NIHR Office for Clinical Research Infrastructure and the NHS National Horizon Scanning Centre.
Identification of novel biomarkers and pathways benefit pharmaceutical industry in two different ways: Identification of new druggable targets and determination of mechanistic markers to identify patient population with disease susceptible for a certain drug ('companion diagnostics').


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